Absence of Association Between Genetic Variation of the β3-Adrenercjic Receptor and Metabolic Pnenotypes in Oji-Cree

Robert A Hegele; Stewart B Harris; Anthony JG Hanley; Husain Azouz; Philip W Connelly; Bernard Zinman

doi:10.2337/diacare.21.5.851

Original Articles

Absence of Association Between Genetic Variation of the β₃-Adrenercjic Receptor and Metabolic Pnenotypes in Oji-Cree

Robert A Hegele, MD,
Stewart B Harris, MD,
Anthony JG Hanley, MSC,
Husain Azouz,
Philip W Connelly, PHD and
Bernard Zinman, MD

Blackburn Cardiovascular Genetics Laboratory, University of Western Ontario London, Ontario, Canada
Robarts Research Institute, and Thames Valley Family Practice Research Unit, University of Western Ontario London, Ontario, Canada
Samuel Lunenfeld Research Institute, University of Toronto Toronto, Ontario, Canada
Mount Sinai Hospital, St. Michael's Hospital, University of Toronto Toronto, Ontario, Canada
Department of Medicine, University of Toronto Toronto, Ontario, Canada
Department of Biochemistry, University of Toronto Toronto, Ontario, Canada

Address correspondence and reprint requests to Robert A. Hegele, MD, Blackburn Cardiovascular Genetics Laboratory, Robarts Research Institute, 406–100 Perth Dr., London, Ontario N6A 5K8, Canada. E-mail: robert.hegele{at}rri.on.ca.

Diabetes Care 1998 May; 21(5): 851-854. https://doi.org/10.2337/diacare.21.5.851

Abstract

OBJECTIVE To assess the association between the common missense variant, Y64R, in the gene encoding the β3-adrenergic receptor, ADRB3, and intermediate phenotypes related to obesity and NIDDM in Canadian Oji-Cree.

RESEARCH DESIGN AND METHODS We determined genotypes of the ADRB3 Y64R polymorphism in 508 clinically and biochemically well-characterized adult Oji-Cree, of whom 115 had NIDDM. We tested for associations with multivariate analysis of variance.

RESULTS We found the ADRB3 R64 allele frequency to be 0.40 in this population, which is the highest yet observed in a human population. Furthermore, 15% of subjects were R64/R64 homozygotes, compared with a virtual absence of homozygotes in European study samples. However, we found no statistically significant associations of the ADRB3 Y64R genotype either with the presence of NIDDM, with indexes of obesity, or with intermediate quantitative biochemical traits related to NIDDM.

CONCLUSIONS Despite the very high frequency of the ADRB3 R64 allele in this sample of aboriginal people, it was not associated with any metabolic phenotype. This suggests that the ADRB3 R64 allele is probably not a major determinant of obesity or NIDDM in these aboriginal Canadians.